CYP2A6 overexpression in human lung cancers correlates with a high malignant status.

CYP2A6 is a major phase I enzyme metabolizing tobacco-specific nitrosamines, implicated as risk factors for lung cancer. In this study, immunohistochemistry and in situ hybridization (ISH) for CYP2A6 with human lung cancer tissues (n=31) obtained by surgical resection showed significantly higher immunoreactivity in the cases with lymph node metastasis. The adenocarcinoma cases (n=23) with lymph node metastasis or large tumor size showed a high immunoreactivity for CYP2A6. The squamous cell carcinoma cases (n=6) with large tumor size showed a tendency for low CYP2A6 immunoreactivity. ISH for CYP2A6 revealed mRNA expression in both adenocarcinoma and squamous cell carcinoma cells. The data suggest that CYP2A6 could have an important role in the development and proliferation of lung carcinomas. With adenocarcinomas, CYP2A6 could be a target candidate for therapeutic and chemopreventive intervention.

Epithelioid malignant peripheral nerve sheath tumor. Report of a case with inflammatory infiltration.

The epithelioid malignant peripheral nerve sheath tumor (EMPNST) is a rare sarcoma originating from the supportive non-neuronal components of peripheral nerves. Our patient was a 75-year-old Japanese man who presented with complaints about pain and a mass in the left thigh. Characteristic histopathological features were large epithelioid-like cells closely resembling a malignant melanoma or another type of soft tissue tumor. Notable infiltration of neutrophils in the tumor was seen. Immunohistochemically, the tumor cells proved positive for S-100, NSE, GFAP, MBP, chromogranin A and synaptophysin, and negative for CEA, keratin, HMB-45, G-CSF, and GM-CSF. Tumor-related inflammatory infiltration may be caused by an autonomous production of some cytokines. However, these tumor cells were negative for G-CSF and GM-CSF so that the mechanism triggering inflammatory infiltration is unclear. Electron microscopy revealed the presence of an extracellular basal lamina, intermediate cell junctions, and numerous dense-cored granules in the cytoplasm. These findings suggested a schwannian derivation, consistent with the diagnosis of EMPNST. There have been reports on S-100 positivity and HMB-45 negativity of this tumor type, but to the best of our knowledge, this is the first description of an EMPNST positive for MBP, chromogranin A, and synaptophisin. Where unequivocal features are lacking, these markers might be useful for differential diagnosis.

Individual risk factors associated with nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae: a Japanese birth cohort study.

BACKGROUND: The first step in a bacterial disease is the establishment of nasopharyngeal carriage. METHODS: We conducted a birth cohort study to identify factors associated with colonization in healthy children and evaluate the serotype distributions and resistances of Streptococcus pneumoniae/Haemophilus influenzae. Nasopharyngeal cultures were obtained from 349 subjects at 5 time points coinciding with health checkups (4, 7, 10, 18 and 36 months). RESULTS: A total of 551 S. pneumoniae (penicillin resistance rate: 46.3%) and 301 H. influenzae (ampicillin resistance rate: 44.5%) isolates were obtained from 1654 samples. In this study, 47.5% and 60.9% of S. pneumoniae isolates were included in the serotypes of 7- and 13-valent pneumococcal conjugate vaccines, respectively. Analyzing by Cox proportional hazards models, cohabiting older sibling(s) attending day-care (hazard ratios: 2.064-3.518, P < 0.001) and an early start of day-care attendance by the subjects themselves (2.259-2.439, P < 0.001) were associated with a higher risk of early colonization regardless of their susceptibility. Recent exposure to antimicrobials was also significantly associated with increased risk of colonization (odds ratios: 2.032-2.999, P < 0.001) but not with resistance rates. This data indicated that introduction of appropriate antimicrobial usage in areas of overuse of antimicrobials could contribute to lower colonization of S. pneumoniae/H. influenzae, resulting in a decrease in the absolute number of resistant isolates. CONCLUSIONS: Strategies to control transmission at day-care centers or from older sibling(s) as well as appropriate use of antimicrobials are essential for reducing colonization and the absolute number of resistant isolates.

Incidence survey of acute otitis media in children in Sado Island, Japan--Sado Otitis Media Study (SADOMS).

BACKGROUND: Acute otitis media (AOM) is one of the most common forms of bacterial infection and cause for clinic visits in children. The incidence of AOM was 0.9-1.2 episodes per person-year during the first 2 years of life in previous reports conducted before 2000. The aim of this study was to 1) evaluate the latest AOM incidence in pediatric outpatients and 2) identify the bacterial pathogens from these patients and ascertain their serotypes and resistance. METHODS: The study was conducted in a closed population, involving all pediatricians and otolaryngologists in Sado Island allowing accurate determination of AOM incidence. In each month, one week was assigned as "surveillance week", and all outpatients with acute illness aged 0-18 years examined during the surveillance weeks were enrolled. AOM was diagnosed on the basis of otoscopic findings and clinical symptoms were recorded. Specimens were collected from the nasopharynx or middle ear cavity of AOM patients and examined for bacteria. Antimicrobial susceptibilities, serotypes, and molecular typing for resistance were determined among Streptococcus pneumoniae and Haemophilus influenzae. RESULTS: In total, 8,283 clinic visits were conducted, and 354 episodes (4.3%, 95% CI: 3.9-4.7%) among 312 children were diagnosed as AOM. The incidence of AOM was highest in children of 1 year of age (0.54 episodes/child/year, 95% CI: 0.44-0.64). Serotype coverage of 7- and 13-valent pneumococcal conjugate vaccines in this study were 38.0% (95% CI: 29.3-47.3) and 62.8% (95% CI: 53.6-71.4), respectively. Of 122 H.influenzae isolates available for typing, 120 were nontypeable and 2 were type b. A high proportion of S. pneumoniae isolates (46%) showed resistance to penicillin. Approximately half of H. influenzae isolates had genetic markers for beta-lactamase-negative ampicillin-resistance. CONCLUSIONS: Approximately 4-5% of pediatric outpatients, even without AOM-related symptoms, had AOM in our study. Pediatricians as well as otolaryngologists should check the tympanic membrane findings of all pediatric outpatients.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated from children in a community with low antimicrobial pressure in Japan.

Sado Island in Japan is an area with low antimicrobial pressure. A total of 41 community-onset methicillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from pediatric outpatients and healthy children between August 2009 and January 2012, and genotyping and antimicrobial susceptibility testing of the MRSA isolates were performed. Additionally, the sources of MRSA isolated from healthy 1-month-old neonates were assessed. All isolates were negative for the Panton-Valentine leukocidin genes. Our data showed a lower prevalence of staphylococcal cassette chromosome (SCC)mecII on Sado Island (31.7% in total and 46.7% in healthy carriage) than that in the other areas of Japan, suggesting that a low level of antimicrobial use may be related to a low SCCmecII carriage rate in the community. To our knowledge, this is the first report of sequence type (ST)81/SCCmecIVg strains as well as the novel ST strain (ST2180/SCCmecIVa) in Japan. In addition, we detected an arginine catabolic mobile element (ACME)-arcA-positive ST764/SCCmecIIa clone that could disseminate successfully in the community. Intrafamilial transmission was observed in neonates identified with the SCCmecIV MRSA strains, and these strains were genetically typed as community-associated MRSA; the transmission routes of the remaining SCCmecIIa MRSA (genetically typed as healthcare-associated MRSA) strains could not be defined. In this study, we have shown that multiple MRSA strains can circulate in a community even under low antimicrobial pressure.